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PubMed2026

Developmental roles of LSD1/KDM1A-like (LDL) proteins in plants.

LYSINE-SPECIFIC DEMETHYLASE 1-like (LDL) proteins are conserved FAD-dependent amine oxidases that serve as pivotal regulators in plants. While animal systems typically rely on a single LSD1/KDM1A enzyme, the Arabidopsis thaliana genome encodes an expanded family of LDL homologues (FLD, LDL1, LDL2, and LDL3), resulting in substantial subfunctionalization and specialized recruitment mechanisms. This review explores the diverse developmental roles of plant LDLs, ranging from flowering time and circadian clock regulation to heterochromatin maintenance and epigenetic regulation. We discuss the redundant roles of FLD, LDL1, and LDL2 in repressing the floral repressor FLC and their nonredundant specialized function within the CCA1/LHY-TOC1 circadian feedback loop. A central focus of our review is the emerging mechanism of transcription-coupled demethylation, in which LDLs associate with the phosphorylated C-terminal domain of RNA polymerase II to modify chromatin cotranscriptionally within gene bodies. By integrating findings from Arabidopsis thaliana and crops such as tomato and soybean, we illustrate how the diversified LDL-mediated regulatory toolkit facilitates precise, gene-specific regulation. Ultimately, the LDL family represents a cornerstone of the sophisticated epigenetic strategies that regulate plant phenotypic plasticity in response to developmental and environmental cues.

Circadian clock↗

PubMed2026

Risk factors of venous thromboembolism in ICU patients: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to identify risk factors associated with the development of VTE in patients admitted to the intensive care unit (ICU). METHODS: A systematic literature search was conducted via PubMed, Embase, Web of Science, and Cochrane databases up to 25 April 2025, to identify studies examining the association between risk factors and the occurrence of venous thromboembolism (VTE) in ICU patients. Data were pooled using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 2465 relevant studies were identified through the systematic search, of which 30 were included in the meta-analysis. The pooled data showed that the following were significant risk factors for venous thromboembolism (VTE) in ICU patients: central venous catheterization (OR = 2.67, 95% CI: 1.67-4.28; I2 = 28%), invasive mechanical ventilation (OR = 2.08, 95% CI: 1.46-2.96; I2 = 0%), advanced age (OR = 2.06, 95% CI: 1.28-3.31; I2 = 86%), length of ICU stay (OR = 4.24, 95% CI: 1.43-12.57; I2 = 98%), malignancy (OR = 2.30, 95% CI: 1.03-5.12; I2 = 67%), elevated D-dimer levels (OR = 2.46, 95% CI: 1.37-4.40; I2 = 34%), and a history of VTE (OR = 2.84, 95% CI: 1.45-5.55; I2 = 51%). According to the GRADE assessment, the quality of evidence was rated as moderate for invasive mechanical ventilation, low for central venous catheterization and D-dimer levels, and very low for the remaining factors. CONCLUSION: Invasive mechanical ventilation, central venous catheterization, and elevated D-dimer levels are associated with VTE risk, supported by relatively high-quality evidence. These findings may help identify ICU patients at higher risk of VTE, inform the development of risk assessment models for patient stratification, and ultimately contribute to improved prognosis through optimal screening and management strategies.

Humans↗

PubMed2026

Effects of hospital planning reforms on access, costs, efficiency, and quality of care in OECD countries: Systematic review and meta-analysis.

BACKGROUND: Many OECD countries have implemented hospital planning reforms to rising healthcare costs, demographic changes, and concerns about access, efficiency, and quality of care. Despite broad implementation, evidence on effectiveness remains fragmented and country-specific. OBJECTIVE: To synthesize evidence on the effects of hospital planning reforms aross four outcome domains: access, costs, efficiency, and quality of care. METHODS: We conducted a systematic review following Cochrane methodology, searching PubMed and Web of Science (January 2000 - September 2025). Studies were categorized into four intervention types - centralization, minimum volume requirements (MVR), performance-based targets, and governance and ownership restructuring. Risk of bias was assessed using Joanna Briggs Institute checklist for quasi-experimental designs. Where data permitted, random-effects meta-analyses pooled standardized mean differences (SMD) for access and efficiency and risk differences (RD) for quality outcomes. RESULTS: 26 studies from 12 countries were included. Centralization increased patient travel distances and reduced length of stay (SMD -0.09, 95% CI -0.17 to -0.01) and complications (RD -14.52 pp, -25.95 to -3.09), and, jointly with performance-based targets, 30-day readmissions (RD -0.43 pp, -0.65 to -0.22). Mortality effects varied by timepoint and intervention: short-term endpoints were largely non-significant, whereas 90-day mortality was reduced under centralization (RD -0.80 pp, -1.25 to -0.35) and 60-day mortality under MVR (RD -2.00 pp, -2.82 to -1.18). Survival was non-significant throughout. No study examined costs. CONCLUSION: The absence of cost evidence is a critical gap. Substantial heterogeneity reflects variation in reform design and context, underscoring the need to interpret findings by intervention and country conditions.

Humans↗

PubMed2026

Attitudes, knowledge, and behavioral control regarding child abuse reporting in middle eastern nursing professionals: A systematic review and meta-analysis.

INTRODUCTION: Child abuse is critically underreported in the Middle East, with up to 90% of cases going unidentified. Nurses play a central role in child protection systems, yet factors influencing their reporting practices in this region have not been comprehensively synthesized. This study aims to review systematically and meta-analyze evidence on Middle Eastern nurses' knowledge, attitudes, and perceived behavioral control regarding child abuse reporting. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines. Five databases (PubMed, Scopus, Web of Science, Embase, Cochrane Library) were searched through November 2025. Studies targeting nursing professionals or students in Middle Eastern countries assessing knowledge, attitudes, intention to report, subjective norms, or perceived behavioral control were included. Random-effects meta-analyses were performed with subgroup analyses comparing students and practicing nurses. RESULTS: Fourteen studies comprising 4018 participants across six countries met the inclusion criteria. The pooled knowledge score was 61.64% (95% CI: 50.14-73.14), with nursing students scoring higher than practicing nurses (75.28% vs. 54.79%, p = 0.03). The pooled attitude score was 60.69% (95% CI: 44.82-76.57). Educational interventions significantly improved knowledge (SMD = 1.54, 95% CI: 0.70-2.38, p = 0.0003). The pooled proportion of nurses intending to report suspected abuse was 75% (95% CI: 0.58-0.92). The pooled subjective norm score was 8.02 (95% CI: 7.75-8.29), and the pooled perceived behavioral control score was 24.34 (95% CI: 22.20-26.46). High heterogeneity (I2 > 95%) reflects substantial variability in educational and legal contexts across the region. CONCLUSIONS: Middle Eastern nurses show moderate knowledge and attitudes toward child abuse reporting, with notable gaps among practicing professionals. Educational interventions are effective but should be integrated with systemic reforms, including mandatory reporting legislation and clear protocols.

Humans↗

PubMed2026

Multi-omics reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function.

Renal fibrosis (RF), a common pathological process driving chronic kidney disease (CKD) progression to end-stage renal failure, is closely associated with oxidative phosphorylation (OXPHOS). Arctigenin (ATG), the main active component of burdock seed, exhibits anti-inflammatory and anti-fibrotic activities, but its mechanisms in RF treatment remain unclear. Here, we performed integrated transcriptomic and proteomic analyses to identify key targets and pathways of ATG in a unilateral ureteral obstruction-induced rat RF model. Multi-omics enrichment analysis revealed that NDUFS8 and NDUFS2 were the core targets of ATG, with the OXPHOS pathway as the central intersecting pathway. Our results suggest that ATG exerts anti-renal fibrosis effects by targeting the OXPHOS pathway to inhibit excessive reactive oxygen species production and oxidative stress. SIGNIFICANCE: Chronic kidney disease (CKD) continues to impose an escalating global health and socioeconomic burden, while renal fibrosis (RF), as the convergent pathological endpoint of virtually all progressive nephropathies, remains the principal determinant of irreversible renal failure and adverse clinical outcomes. Despite extensive efforts to develop antifibrotic therapies, effective clinical interventions remain elusive, largely due to the complex and multifactorial nature of RF pathogenesis. In this study, we employed an integrated multi-omics framework encompassing transcriptomics, proteomics, and metabolomics to systematically decipher the antifibrotic mechanism of arctigenin (ATG), a bioactive natural compound derived from traditional Chinese medicine. Our findings identify mitochondrial oxidative phosphorylation as the pivotal regulatory axis underlying the renoprotective effects of ATG and further establish key catalytic subunits of mitochondrial complex I as its direct molecular targets. Mechanistically, ATG not only restores complex I activity and reprograms mitochondrial energy metabolism but also preserves the intracellular stability and localization of these subunits, thereby preventing their aberrant release-mediated inflammatory activation and disrupting the self-perpetuating cycle linking metabolic dysfunction, inflammation, and fibrosis progression. Beyond revealing a previously unrecognized dual mechanism integrating metabolic and inflammatory regulation, this study provides compelling evidence that mitochondrial dysfunction is not merely a secondary consequence of tissue injury but a fundamental driver of fibrotic remodeling. Importantly, our work highlights the translational potential of natural product-based mitochondrial interventions for CKD treatment and supports a broader conceptual shift toward metabolism-centered therapeutic strategies for chronic fibrotic diseases. Given the central role of mitochondrial dysfunction across multiple organs, these findings may also have far-reaching implications for the treatment of systemic fibrosis-related disorders beyond the kidney.

Animals↗

PubMed2026

Changes in heroin-related ambulance attendances following the introduction of a medically supervised injecting room in Victoria, Australia.

BACKGROUND: Injecting drug use contributes significantly to morbidity, mortality and broader social harms globally. Supervised Injecting Facilities (SIFs) are harm reduction interventions that reduce overdose risk and facilitate access to health services for marginalised individuals. While international evidence supports the effectiveness of SIFs, Australian population-level surveillance data quantifying their impact on emergency medical service utilisation remain limited. METHODS: Using data from the National Ambulance Surveillance System, we conducted a retrospective, interrupted time series analysis of heroin-related ambulance attendances within the local catchment of the Medically Supervised Injecting Room (MSIR) between January 2015 and December 2023. Supplementary analysis included comparisons with central Melbourne suburbs and the broader state of Victoria. Key intervention timepoints, including the opening of the MSIR on 30 June 2018, expansion of its operating hours in July 2019, and the COVID-19 pandemic from April 2020 to October 2021, were examined to assess changes in heroin-related attendances over time. Segmented regression models were used to assess changes in heroin-related ambulance attendance trends over time. RESULTS: At the time the MSIR opened, the model-predicted heroin-related ambulance attendance rate within the MSIR catchment was 123 per 100,000 population per month, equivalent to approximately 48 heroin-related ambulance attendances per month. Prior to implementation, the attendance rate was increasing by an estimated 0.74 per 100,000 population per month. Following the opening of the MSIR, the previously increasing trajectory reversed, with ambulance attendance rates declining by approximately 2.3 per 100,000 population per month relative to the pre-intervention trend. By the end of the study period (December 2023), the predicted monthly heroin-related ambulance attendance rate had declined to 36 per 100,000 population (approximately 14 attendances per month), representing an overall reduction of 70.7% from the time of MSIR implementation. These reductions persisted throughout the COVID-19 lockdown period and were sustained after restrictions lifted. Supplementary analysis showed no comparable reductions in the central Melbourne region or the remainder of Victoria. CONCLUSIONS: The introduction of the MSIR in Richmond was associated with a sustained reduction in heroin-related ambulance attendances within its catchment area. These findings provide strong population-level evidence that SIFs reduce acute heroin-related harms requiring emergency ambulance response, reinforcing their role as an effective harm reduction strategy within the Australian context.

Humans↗

PubMed2026

Plant cis-regulatory grammar: Decoding the multidimensional code of transcriptional regulation for programmable crop engineering.

Cis-regulatory elements (CREs) orchestrate the spatiotemporal precision of gene expression that underlies plant development, adaptation, and domestication. Decoding the cis-regulatory grammar of plant genomes remains a central challenge in modern biology, with profound implications for programmable crop engineering. Here, recent conceptual and technological advances are synthesized to reshape our understanding of plant CREs. This review first argues that CRE function is not only an intrinsic property of DNA sequence alone but also emerges from a multidimensional context, including chromatin accessibility, histone modifications, three-dimensional genome topology, and cell type-specific regulatory landscapes. Furthermore, the convergence of single-cell epigenomics, high-throughput functional assays, and CRISPR-based dissection has begun to unravel this contextual grammar, revealing the computational principles governing transcriptional regulation. Critically, we propose that artificial intelligence (AI) platforms are catalyzing an ongoing transition from descriptive discovery to predictive engineering, wherein these platforms outperform natural evolution in designing synthetic CREs. Finally, a roadmap is outlined toward a plant regulatory grammar foundation model, which will enable truly predictive engineering of gene expression when fine-tuned for specific tasks. Collectively, the integration of single-cell resolution maps, precise genome editing, AI-driven design, and regulatory-compliant delivery systems promises to transform our ability to reprogram plant gene regulation for next-generation agriculture, bridging the gap between foundational regulatory biology and tangible crop improvement.

artificial intelligence↗

PubMed2026

Beyond species trees: pervasive gene flow limits phylogenomic resolution in the diversification of Juniperus from the Qinghai-Tibet Plateau.

Understanding how lineages diversify despite persistent ancestral polymorphism and recurrent gene flow remains a central challenge in evolutionary biology. Juniperus distributed across the Qinghai-Tibet Plateau provide an ideal system for addressing this question because repeated geological uplift and climatic oscillations have likely promoted cycles of lineage divergence, range shifts, and secondary contact. Here, we combined approximately 1.08 million genome-wide SNPs from 164 individuals representing thirteen Juniperus lineages with phylogenomic datasets comprising 3,381 nuclear single-copy genes and nearly complete plastomes. We detected extensive phylogenomic discordance and cytonuclear incongruence across genomic datasets. Topology weighting, coalescent simulations, quartet-based tests, and analyses of gene flow and reticulation collectively support the interpretation that these patterns were shaped by the combined effects of prolonged incomplete lineage sorting and gene flow during lineage diversification. Ecological niche analyses further provide a spatial and climatic context in which environmentally similar lineages may have had greater opportunities for secondary contact during historical range shifts. Collectively, our results reveal that the evolutionary history of Qinghai-Tibet Plateau Juniperus is characterized by reticulate diversification rather than strictly bifurcating evolution, and demonstrate how genome-wide discordance can provide biological insights into the evolutionary processes underlying lineage diversification.

Gene Flow↗

PubMed2026

Characteristics of p53 and Smad4 immunohistochemistry in pancreatic ductal adenocarcinoma and validation by next-generation sequencing.

BACKGROUND: Mutations in four major driver genes -KRAS, CDKN2A, TP53, and SMAD4- are central to the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) and critically inform diagnosis, therapeutic decision-making, and prognostic assessment. Although next-generation sequencing (NGS) is widely regarded as the gold standard for detecting these mutations, its clinical application is often limited by suboptimal analytical efficiency and substantial economic cost. Among these genes, immunohistochemical (IHC) staining for the proteins encoded by TP53 and SMAD4 has been extensively adopted in routine pathology practice. However, standardized IHC pattern classification schemes and rigorous validation of their predictive accuracy for underlying genomic alterations remain lacking in PDAC. METHODS: We retrospectively enrolled 63 PDAC patients and systematically characterized the typical IHC expression patterns of p53 and Smad4. Targeted NGS was subsequently performed on all available tumor specimens, and the resulting mutational profiles were correlated with corresponding IHC findings. Diagnostic performance including sensitivity, specificity and accuracy of p53 IHC for predicting TP53 mutations and of Smad4 IHC for predicting SMAD4 mutations was rigorously evaluated. RESULTS: Among the four canonical driver genes, co-occurring double- or triple-gene mutations were prevalent; within TP53 and SMAD4, missense mutations constituted the most frequent variant type. Using NGS as the reference standard, we validated the diagnostic utility of a three-tiered p53 IHC classification system, particularly in fine-needle biopsy (FNB) specimens. Furthermore, we proposed a novel, refined Smad4 IHC pattern classification that incorporates an "intermediate" category, thereby expanding upon conventional binary interpretation. This new scheme achieved markedly improved mutation prediction accuracy (0.76) compared with traditional approaches (0.57). CONCLUSION: Our study highlights the complementary diagnostic value of p53 and Smad4 IHC relative to molecular testing in PDAC, especially when tissue is limited, as commonly encountered in FNB specimens. The newly established Smad4 IHC classification system, which integrates an intermediate expression category into the conventional two-tier framework, demonstrates superior clinical utility and enhances predictive accuracy for SMAD4 genomic alterations.

Humans↗

PubMed2026

Comparative genomic and proteomic analysis reveals orthogroup structured evolution of tick protease inhibitors.

Protease inhibitors (PIs) play central roles in regulating endogenous proteolysis and host-parasite interactions in ticks. However, the evolutionary architecture underlying their diversification across tick lineages remains insufficiently resolved. Here, we performed a genome-wide comparative analysis of predicted proteomes from 14 tick species to systematically characterize PI repertoires. In total, 4931 putative PIs were identified and grouped into 20 families using the MEROPS classification system. Further, PI families such as Antistasin, WAP-type, and Pacifastin, which have not previously been systematically reported in tick genomes, were classified. Orthogroup inference demonstrated that PI expansion is structured at the level of evolutionary lineages rather than uniformly across families. By stratifying orthogroups according to duplication burden and taxonomic conservation, we identified a broadly conserved single-copy core under strong purifying selection. Motif level analysis of serpin reactive center loops further revealed conservation of inhibitory specificity within single copy orthogroups and diversification of key functional residues in duplication-associated lineages. Integration of secretion prediction and tissue-resolved proteomics from Hyalomma anatolicum and Rhipicephalus microplus demonstrated that evolutionary stratification is reflected at the protein level. Together, these findings provide an orthogroup-resolved evolutionary framework linking duplication dynamics, molecular evolution, and tissue-level protein deployment. This integrative approach offers a systematic basis for prioritizing conserved and diversified PI lineages for future functional and anti-tick intervention studies.

Animals↗

PubMed2026

One Year After a Cyberattack: Lessons Learned and Dosimetric Analysis of Contingency Radiotherapy Plans.

PURPOSE: Cyberattacks on health care institutions pose significant risks to patient care, particularly in radiotherapy departments, which are heavily reliant on digital systems. This study examines the impact of a ransomware attack on our hospital and evaluates the effectiveness of the contingency measures implemented to resume radiotherapy treatments. METHODS AND MATERIALS: Following the cyberattack, our radiotherapy department faced a complete shutdown. After an initial estimate considering a shutdown of several weeks, a contingency plan was executed, including manual patient data retrieval and collaboration with a backup hospital. Contingency plans were prepared and delivered within hours, despite a partial lack of information. These plans allowed some patients to restart treatment 3 days after the attack. A dosimetric analysis was performed for the contingency plans, including various pathologies, mainly glioblastoma, head and neck cancers, and lung cancer. We compared the original and contingency plans in terms of dose coverage to the clinical target volume, biological effective dose, and their clinical impact as assessed at the 1‑year follow‑up after the cyberattack. RESULTS: Treatments resumed within 12 days at our hospital. Patients with glioblastoma showed good target coverage because of generous margins, resulting in favorable outcomes. In head and neck cases, the lack of detailed imaging led to significant target volume misses, suggesting that more conservative initial treatments could have been beneficial. Lung cases demonstrated accurate peripheral lesion targeting but faced challenges in central lesions because of the absence of positron emission tomography information. In most cases, the approach of using a contingency plan, even with limited information, led to a higher biological effective dose than would have been achieved if treatment had been stopped until full recovery at our hospital. CONCLUSIONS: The study highlights the critical importance of robust contingency planning in radiotherapy departments, emphasizing the need for backup systems and tailored approaches based on tumor location and available diagnostic information. These lessons emphasize that preparedness for digital disruptions should not focus exclusively on information and technology infrastructure.

Humans↗

PubMed2026

Proteomics-based analysis of the defense mechanisms of disease-resistant grass carp against Aeromonas veronii.

Sustainable aquaculture of grass carp (Ctenopharyngodon idella, GC) is consistently threatened by bacterial diseases, particularly those caused by Aeromonas veronii. A disease-resistant grass carp (DR-GC) has been developed by backcrossing female gynogenetic GC with normal male GC, exhibiting improved resistance. However, the systemic molecular mechanisms of DR-GC defending against Aeromonas veronii infection remain largely unexplored. Here, a label-free quantitative proteomics approach was employed to systematically compare proteomic profiles across five tissues (intestine, liver, muscle, skin, and kidney) in DR-GC and GC under healthy and infected conditions. The intestine was identified as the central defense tissue, exhibiting the highest number of differentially abundant proteins (DAPs). In DR-GC, A0A3N0YEK7 (small ribosomal subunit protein eS28), A0A3N0YGT8 (ATP synthase-coupling factor 6) and A0A3N0YNS7 (apolipoprotein A-I) were significantly upregulated in intestine, while D5KZW6 (GCHV-induced protein), A0A3N0Z0A1 and Q8JH84 (hemoglobin subunit alpha) were significantly dysregulated across multiple tissues, which playing the critical roles in defense mechanisms at the protein level. Furthermore, cytochrome P450-associated pathways, cytosolic DNA-sensing and RIG-I-like receptor signaling pathways were identified as crucial coordinators mediating immune and metabolic responses. This study provides the first comprehensive proteomic view of multi-tissue defense mechanisms in DR-GC, and identifies key DAPs and pathways for subsequent functional validation.

Animals↗

PubMed2026

Tissue-derived extracellular matrix hydrogels instruct epigenetic adaptation in metastatic colonization.

The extracellular matrix (ECM) plays a central role in regulating tumor progression and metastatic colonization by providing biochemical and mechanical signals that shape cancer cell fate. However, most organoid culture systems rely on basement membrane extracts that fail to reproduce the tissue-specific extracellular environments encountered during metastasis. Here, we develop tissue-derived decellularized matrix hydrogels to reconstruct organ-specific microenvironments and investigate epigenetic adaptation to ECM cues during metastatic colonization. Patient-derived colorectal cancer organoids cultured in colon-derived matrices exhibited enhanced maintenance of stem-like phenotypes and colon-specific chromatin accessibility landscapes compared with cultures grown in basement membrane extracts, demonstrating improved physiological relevance for primary tumor modeling. When exposed to matrices derived from secondary organs, the organoids showed distinct growth phenotypes accompanied by rapid, tissue-dependent chromatin accessibility remodeling, indicating that ECM composition alone can reshape regulatory programs governing metastatic adaptation. Notably, liver-derived matrices selectively activated hepatocyte nuclear factor 4 alpha (HNF4A)-associated transcriptional networks and created a context-specific dependence on c-MET signaling for survival. Functional perturbation of HNF4A or c-MET signaling confirmed that both are required for organoid formation specifically within the liver matrix environment. Together, these findings establish tissue-derived matrix hydrogels as instructive bioactive materials that actively regulate cancer cell epigenetic states and reveal microenvironment-specific therapeutic vulnerabilities during early metastatic colonization.

Journal Article↗

PubMed2026

Electroencephalographic evidence of cortical network disruption preceding overt cardioinhibition during tilt-induced reflex syncope.

OBJECTIVE: Reflex syncope is a common cause of transient loss of consciousness. However, the early cerebral mechanisms underlying cardiovascular changes remain poorly understood. Our objective was to investigate early cerebral changes by quantitatively analyzing EEG activity preceding overt cardioinhibition during tilt-induced reflex syncope. METHODS: EEG recordings from patients undergoing tilt testing were retrospectively analyzed. Patients who experienced reflex syncope were compared to those who did not. Spectral and functional connectivity analyses were performed across baseline, pre-cardioinhibition, and syncopal phases. RESULTS: Prior to the onset of cardioinhibitory pathological reflex, a significant increase in theta-band spectral power was observed in the right temporal region, accompanied by a widespread increase in functional connectivity within the same frequency band. These findings suggest the involvement of brain networks before cardioinhibition. CONCLUSIONS: EEG changes in the theta band (power and functional connectivity) were observed before overt cardioinhibition during tilt-induced reflex syncope. SIGNIFICANCE: Our findings support the hypothesis of cortical processing preceding cardioinhibition in reflex syncope. EEG may represent a valuable complementary tool for improving the understanding and diagnosis of these events.

Humans↗

PubMed2026

Synergistic transcriptional modules in Trichoderma asperellum enhance glutathione detoxification to counteract fungal pathogen toxins.

Trichoderma fungi are potent biocontrol agents. However, their defence mechanisms against pathogen-derived toxins remain poorly understood. We identified two synergistic transcription factor modules in T. asperellum that orchestrate the detoxification of cytotoxic secondary metabolites from the poplar blight pathogen Alternaria alternata. Overexpression of the central regulator TasMYB46 reduced disease lesion area by approximately 22% and was associated with decreased pathogen-induced reactive oxygen species (ROS) accumulation. Mechanistically, TasMYB46 directly activates the glutathione S-transferases TasGST61.1 and TasGST56.1 through distinct promoter binding sites (G-box/as-1/MBS), forming dedicated detoxification modules. Crucially, we identified urolithin C as the most abundant phytotoxin in A. alternata metabolites, which is efficiently detoxified through the TasMYB46-TasGST61.1 module. The transcription enhancer TasbHLH53.8 amplifies this system by binding to TasMYB46, boosting TasGST expression and enhancing glutathione-dependent detoxification capacity. This coordinated response elevates glutathione pools and antioxidant enzyme activities (GST/GPx), conferring increased oxidative stress resistance. This study reveals a novel defence mechanism in Trichoderma in which MYB-bHLH-GST modules enable biocontrol agents to neutralise pathogen-derived toxins. Given that Alternaria toxins threaten crops globally (tomatoes, potatoes, citrus), the discovered regulatory synergy represents a strategic advance in developing next-generation biocontrol solutions against toxin-producing plant pathogens.

Alternaria↗

PubMed2026

Utility of hearing aid use on neurocognitive functions and auditory processing: A systematic review.

PURPOSE: Hearing loss not only affects the peripheral auditory system but also leads to changes in central auditory pathways and neurocognitive skills. The use of hearing aids has shown potential benefits in mitigating the adverse effects of hearing loss. Earlier literature showed various studies assessing the impact of hearing aid use on cognitive functions and auditory processing, a comprehensive review of the existing literature is warranted. Existing literature showed heterogeneous outcomes among studies investigated the effect of Hearing aid use in combating the adverse effects of hearing loss on neurocognitive functions and auditory processing. METHOD: Databases including PubMed, SciELO, Cochrane Library, PsycINFO, Web of Science, and Index Copernicus were searched (2005-2025) using English keywords on hearing aid effects on neurocognition and auditory processing in individuals with hearing loss. Studies on effect of hearing aid use on neurocognition and auditory processing were included, while those involving cochlear implant users or other neurological disorders unrelated to hearing loss were excluded. Titles, authors and publication years were examined, and duplicates were removed. RESULTS: Total of 61 research papers were found on specific area and were included in the present review. Findings of these 61 articles have been analysed and are reported in this article. The outcome of the present study showed usefulness of hearing aid use on neurocognitive functions and auditory processing. CONCLUSION: The present literature review emphasized the importance of early rehabilitation through hearing aid use to alleviate the adverse effects of hearing loss on neurocognitive function and auditory processing.

Humans↗

PubMed2026

Association Between 24-Hour Blood Pressure and Rates of Retinal Nerve Fiber Layer Progression in Glaucoma: The Vascular Imaging in Glaucoma Study.

PURPOSE: Low systemic blood pressure (BP) has been implicated as a risk factor for glaucoma progression. The purpose of this study was to investigate the association between 24-hour BP and rates of retinal nerve fiber layer (RNFL) loss in eyes with primary open-angle glaucoma. DESIGN: Prospective cohort study. PARTICIPANTS: Seventy-nine eyes from 42 subjects with glaucoma (mean age, 68.5 ± 7.6 years) enrolled in the Vascular Imaging in Glaucoma Study at the Bascom Palmer Eye Institute. METHODS: Participants underwent 24-hour ambulatory BP monitoring at baseline. Follow-up evaluations were conducted at 4-month intervals and included ophthalmic examination, BP measurement, and peripapillary RNFL thickness measurement with spectral-domain optical coherence tomography. The association between BP and RNFL loss over time was assessed using linear mixed-effects models adjusted for age, sex, race, baseline RNFL thickness, central corneal thickness, and intraocular pressure. MAIN OUTCOME MEASURES: The effect of baseline 24-hour mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP) on the rate of average RNFL loss over time. RESULTS: Eyes underwent an average of 13 ± 3 optical coherence tomography exams over 43 ± 10 months of follow-up. The mean rate of RNFL loss was -0.34 ± 0.64 µm/y (median: -0.32; interquartile range: -0.66 to -0.04 µm/y). After adjusting for confounding factors, every 10 mm Hg lower in 24-hour minimum MAP, SBP, and DBP was associated with -0.542 µm/y (P < .001), -0.360 µm/y (P = .003), and -0.458 µm/y (P = .008) faster RNFL loss, respectively. Eyes in the lowest quartile of average 24-hour MAP (81-90 mm Hg) and minimum 24-hour DBP (35-47 mm Hg) experienced significantly faster progression compared to those in the highest quartile, with differences of -0.68 µm/y (P = .017) and -0.63 µm/y (P = .030), respectively. CONCLUSIONS: Lower systemic BP, especially minimum MAP, SBP, and DBP measured by 24-hour ambulatory BP monitoring, is associated with faster rates of RNFL loss in primary open-angle glaucoma eyes. 24-hour BP monitoring may help predict glaucoma patients at greater risk of progression.

Humans↗

PubMed2026

Innovation-related perception as a key driver of alternative protein acceptance: evidence from an early-stage model for cultivated meat and algae-/microalgae-based alternative protein products in Italy.

Alternative proteins are increasingly considered part of the transition toward more sustainable food systems, yet their diffusion depends critically on consumer acceptance. This study investigates the early-stage acceptance of two alternative protein categories in Italy-cultivated meat and algae-/microalgae-based alternative protein products. Focusing on the first three phases of acceptance, the analysis examines how innovation-related perception (IRP) shapes consumer perceived value (CPV), consumer perceived risk (CPR), and subsequent affective (AFF), cognitive (COG), and conative (CON) responses. Data were collected through an online survey administered to 238 Italian respondents and analysed using partial least squares structural equation modelling (PLS-SEM). The results show that IRP is the main upstream driver of early-stage acceptance in both product domains: more favourable perceptions strongly increase perceived value and reduce perceived risk. In turn, CPV exerts a much stronger influence than CPR on both affective and cognitive attitudes. A tentative cross-model comparison suggests only a descriptive variation in the final transition toward conative acceptance: affective and cognitive responses were both significant in the two models, with a relatively larger affective coefficient for cultivated meat and more balanced coefficients for algae-/microalgae-based products. Overall, the findings support a process-based interpretation of alternative protein acceptance and highlight the central role of innovation-related perception in shaping early consumer responses. These results provide relevant implications for communication strategies, product positioning, and policy actions aimed at improving the acceptability of alternative proteins in food cultures characterised by strong culinary traditions.

Italy↗